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A checkpoint on the road to cancer

Nature volume 392, pages 223–224 (1998)Cite this article

Mutations that disrupt a cell-division checkpoint, thereby causing alterations in chromosome number, have been identified in cancer cells. The accompanying increase in mutability helps to explain how tumours acquire large numbers of mutant genes during their development.

For the past two decades, cancer researchers have grappled with a paradox. The appearance of a human tumour is the culmination of a complex, multi-step process. The rate-limiting steps seem to be mutations in a half-dozen or more cellular genes that, directly or indirectly, affect tumour cell proliferation. However, from calculations using the known mutation rate in non-germline cells (∼10−7 per gene per cell generation), one can predict that so many mutant genes would never accumulate in the genome of cell lineage during a human lifetime1,2. Hence, tumour formation is mathematically impossible. In the immortal words of the Maine farmer, answering a visitor's query for directions, “Ye cahn't get theah from heah”. But experiments described by Cahill et al.3 on page 300 of this issue provide a road map to solving this paradox. They show that control mechanisms that ensure the proper separation of chromosomes during cell division can be defective in colorectal cancer cells.

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Figure 1: Normal separation of chromosomes during cell division (mitosis).
Figure 2: How assembly of the mitotic spindle is normally monitored to ensure chromosomal stability.

References

  1. Loeb, L. A. Cancer Res. 51, 3075–3079 (1991).

    Google Scholar 

  2. Loeb, L. A., Springgate, C. F. & Battula, N. Cancer Res. 34, 2311–2321 (1974).

    Google Scholar 

  3. Cahill, D. P. et al. Nature 392, 300–303 (1998).

    Article  ADS  CAS  Google Scholar 

  4. Eshleman, J. R. & Markowitz, S. D. Curr. Opin. Oncol. 7, 83–89 (1995).

    Google Scholar 

  5. Kouri, M. et al. Cancer 65, 1825–1829 (1990).

    Google Scholar 

  6. Frei, J. V. Cancer 69, 1108–1111 (1992).

    Google Scholar 

  7. Ionov, Y., Peinado, M. A., Malkhosyan, S., Shibata, D. & Perucho, M. Nature 363, 558–561 (1993).

    Article  ADS  CAS  Google Scholar 

  8. Thibodeau, S. N., Bren, G. & Schaid, D. Science 260, 816–819 (1993).

    Google Scholar 

  9. Aaltonen, L. A. et al. Science 260, 812–816 (1993).

    Google Scholar 

  10. Rieder, C. L., Cole, R. W., Khodjakov, A. & Sluder, G. J. Cell Biol. 130, 941–948 (1995).

    Google Scholar 

  11. Hoyt, M. A., Totis, L. & Roberts, B. T. Cell 66, 507–517 (1991).

    Google Scholar 

  12. Li, R. & Murray, A. Cell 66, 519–531 (1991).

    Google Scholar 

  13. Hardwick, K. G., Weiss, E., Luca, F. C., Winey, M. & Murray, A. W. Science 273, 953–956 (1996).

    Google Scholar 

  14. Taylor, S. S. & McKeon, F. Cell 89, 727–735 (1997).

    Google Scholar 

  15. Li, Y. & Benezra, R. Science 274, 246–248 (1996).

    Google Scholar 

  16. Hwang, L. H. et al. Science 279, 1041–1044 (1998).

    Google Scholar 

  17. Kim, S. H., Lin, D. P., Matsumoto, S., Kitazono, A. & Matsumoto, T. Science 279, 1045–1047 (1998).

    Google Scholar 

  18. Lengauer, C., Kinzler, K. W. & Vogelstein, B. Nature 386, 623–626 (1997).

    Article  ADS  CAS  Google Scholar 

  19. Nowell, P. C. Science 194, 23–28 (1976).

    Google Scholar 

Download references

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Authors and Affiliations

  1. the Whitehead Institute for Biomedical Research and the Department of Biologya, MIT, Cambridge, 02142-1479, Massachusetts, USA

    Terry L. Orr-Weaver & Robert A. Weinberg

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  1. Terry L. Orr-Weaver
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  2. Robert A. Weinberg
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Orr-Weaver, T., Weinberg, R. A checkpoint on the road to cancer. Nature 392, 223–224 (1998). https://doi.org/10.1038/32520

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